Some morbidly obese people are missing genes, new research shows

8:34 February 3, 2010

According to the new findings, around seven in every thousand morbidly obese people are missing a part of their DNA, containing approximately 30 genes. The researchers did not find this kind of genetic variation in people of normal weight.

Morbidly obese people, who have a Body Mass Index (BMI) of over 40, make up slightly more than 2 per cent of North Americans. Researchers believe that the weight problems of around one in 20 morbidly obese people are due to known genetic variations, including mutations and missing DNA. Many more similar obesity-causing mutations, such as the one in this study, remain to be found, the team says.

Previous research had identified several genetic variations that contribute to obesity, most of which are single mutations in a person’s DNA that change the function of a gene. Today’s research is the first to clearly demonstrate that obesity in otherwise physically healthy individuals can be caused by a rare genetic variation in which an individual’s DNA is missing. The researchers do not yet know the function of the missing genes, but previous research has suggested that some of them may be associated with delayed development, autism and schizophrenia.

People inherit two copies of their DNA, one from their mother and one from their father. Sometimes, missing one copy of one or several genes – as in the individuals identified in this latest study – can have a drastic effect on the body.

The researchers believe there may be other genetic deletions, in addition to those identified today, that increase a person’s risk of becoming obese. They hope that by identifying genetic variations causing people to be extremely obese, they can develop genetic tests to help determine the best course of treatment for these individuals.

Professor Philippe Froguel, lead author of the study from the School of Public Health at Imperial College London, said: “Although the recent rise in obesity in the developed world is down to an unhealthy environment, with an abundance of unhealthy food and many people taking very little exercise, the difference in the way people respond to this environment is often genetic. It is becoming increasingly clear that for some morbidly obese people, their weight gain has an underlying genetic cause. If we can identify these individuals through genetic testing, we can then offer them appropriate support and medical interventions, such as the option of weight loss surgery, to improve their long-term health.”

The next step in this research will be to determine the function of the missing genes. Since previous studies have suggested that some of the genes may be associated with delayed development, autism and schizophrenia, the researchers also plan to investigate the possible links between these conditions and obesity.

According to first author Dr Robin Walters, from the School of Public Health at Imperial College London, there are likely to be many more variations like the deletion identified in this study that remain to be found. He said: “Although individually rare, the combined effect of several variations of this type could explain much of the genetic risk for severe obesity, which is known to run in families. Previously identified genetic influences on weight gain have a much less drastic effect – increasing weight by just one or two pounds, for example. By looking at groups of people with severe obesity, we may be more likely to find these rare genetic variations.”

Dr. Robert Sladek, of McGill University and the Génome Québec Innovation Centre in Montreal, added: “In the past three years, we have made fantastic progress in learning how common genetic changes can lead to chronic diseases like diabetes as well as to small differences in people’s weight and height. The genetic change identified in this study is much less common, but leads to much more substantial changes in the body weight of the individuals that it affects.”

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